P1064: CIRCULATING CYTOKINE LEVELS IN PATIENTS WITH PHILADELPHIA-NEGATIVE MYELOPROLIFERATIVE NEOPLASMS – PROFILE AND CLINICAL CORRELATIONS – A SINGLE CENTER STUDY
Authors: G. Tsvetkova, S. Mihailova, N. Ivanov, M. Ivanova, E. Bekirova, G. Balatzenko, A. Vlahova, E. Hadjiev
Journal: HemaSphere (2022)

Background: Myeloproliferative neoplasms(MPNs) are a group of disorders with heterogeneous features and often progressive clinical course. Over the past few years a remarkable advance has been made in the knowledge on the pathogenesis and therapeutic management of the Philadelphia(Ph)-negative MPNs. Despite the wide variety of studies in this field, there are still unsolved issues regarding their biology, disease course, prognosis and treatment. The improved recognition of molecular markers is not sufficient for a comprehensive explanation of the variable clinical symptoms and complications among these patients. The role of the chronic inflammation has been widely considered as a co-factor, involved in the pathogenesis and progression of MPNs. Aims: To analyze the serum levels of a panel of cytokines, associated with the mechanisms of chronic inflammation, among patients with Ph-negative MPNs and healthy controls and the possible correlations of these cytokines with the disease’s features. Methods: One hundred and fifty adults were included in the study, distributed in comparable groups, as follows: 36 patients with Essential thrombocytemia (ET), 49 patients with Polycythemia vera (PV), 30 patients with Myelofibrosis (MF) and 35 age-matched healthy controls. The patients with MPNs were diagnosed according to the latest WHO criteria. The cytokines’ levels were tested in serum samples with a specific kit Cytokine Human Panel for Luminex™. Assessments of the symptoms burden were performed with MPN-SAF- questionnaire. Results: Among the 11 tested cytokines we detected significantly higher serum levels of Interleukin-2, Interleukin-5, Interleukin-6, Interleukin-8, Interleukin-18 and GM-CSF among the MF patients (p<0.05), in comparison with the healthy controls, as well as significantly higher levels of Interleukin-6 in the MF-group, compared to the PV-patients. Elevated serum Interleukin-6, Interleukin-8, Interleukin-18 and GM-CSF were observed in the ET-group versus the control group levels (p<0.05). The cytokine profile analysis also revealed higher serum levels of Interleukin-2, Interleukin-5, Interleukin-6 and Interleukin-18 in the patients with PV, than in the healthy subjects. In terms of estimation of the clinical impact of the circulating inflammatory cytokines among the analyzed MPN cohort - for the ET-patients a positive correlation was present between GM-CSF and the fatigue severity and between Interleukin-6 levels and the weight loss severity index, both assessed according to the MPN-SAF score. A positive correlation was detected between Interleukin-10 levels and the bone pain burden and the degree of weight loss for the patients with MF. Interleukin-18 values demonstrated a positive correlation with the weight loss among the patients with PV. Summary/Conclusion: Our single center study results can give a ground to assume the potential role of the chronic inflammation and the pathogenetic impact of the circulating inflammatory cytokines on the MPNs clinical features and course. The cytokine profile of the different subgroups of MPNs is a topic of interest and can be monitored as a potential predictor of disease progression. It can motivate future research attempts, aiming to alter the clinical evolution of MPNs by affecting the pathogenetic mechanisms of the inflammatory process. It can create prerequisites for future studies regarding more effective therapeutic targets, related to both – the molecular pathways of the mutations in MPNs and the molecular mechanisms of the chronic inflammation.